Neural Stem Cell-Based Therapies and Glioblastoma Management: Current Evidence and Clinical Challenges

Abstract

Gliomas, which account for nearly a quarter of all primary CNS tumors, present significant contemporary therapeutic challenges, particularly the highest-grade variant (glioblastoma multiforme), which has an especially poor prognosis. These difficulties are due to the tumor's aggressiveness and the adverse effects of radio/chemotherapy on the brain. Stem cell therapy is an exciting area of research being explored for several medical issues. Neural stem cells, normally present in the subventricular zone and the hippocampus, preferentially migrate to tumor masses. Thus, they have two main advantages: They can minimize the side effects associated with systemic radio/chemotherapy while simultaneously maximizing drug delivery to the tumor site. Another feature of stem cell therapy is the variety of treatment approaches it allows. Stem cells can be genetically engineered into expressing a wide variety of immunomodulatory substances that can inhibit tumor growth. They can also be used as delivery vehicles for oncolytic viral vectors, which can then be used to combat the tumorous mass. An alternative approach would be to combine stem cells with prodrugs, which can subsequently convert them into the active form upon migration to the tumor mass. As with any therapeutic modality still in its infancy, much of the research regarding their use is primarily based upon knowledge gained from animal studies, and a number of ongoing clinical trials are currently investigating their effectiveness in humans. The aim of this review is to highlight the current state of stem cell therapy in the treatment of gliomas, exploring the different mechanistic approaches, clinical applicability, and the existing limitations.

Exosomes in Parkinson: Revisiting Their Pathologic Role and Potential Applications

“…Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can be isolated from several tissues, including bone marrow (BM), adipose tissue, umbilical cord (UC), and placenta, because of their anti-inflammatory, anti-apoptotic and immunomodulatory properties. MSCs have been used in clinical trials for various disorders, including NDDs [199,200]. In addition, EXOs derived from MSCs have been considered effective for treating various pathological conditions, including CNS disorder, and their ability to rescue dopaminergic neurons in neurotoxic synthetic organic compound 6-hydroxydopamine (6-OHDA) mice models of PD.…”

Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review)

“…These findings demonstrated the feasibility and efficacy of using an NSC-based delivery system. It is noteworthy that researchers have observed a close contact (possibly physical) between NSCs and glioma cells through the use of immunohistochemistry and fluorescence immunohistochemistry (107)(108)(109)(110)(111). More importantly, Benmelouka et al (108) observed that the transplanted NSCs were capable of differentiating into neurons, astrocytes and oligodendrocytes in vivo.…”

“…It is noteworthy that researchers have observed a close contact (possibly physical) between NSCs and glioma cells through the use of immunohistochemistry and fluorescence immunohistochemistry (107)(108)(109)(110)(111). More importantly, Benmelouka et al (108) observed that the transplanted NSCs were capable of differentiating into neurons, astrocytes and oligodendrocytes in vivo. Therefore, NSCs may incorporate into the neuron-glioma circuit or neuron-glial network and form NGSs between neurons and gliomas.…”

EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy

“…Gliomas, which consist of a group of heterogeneous brain tumors originating from three types of glial cells, namely astrocytes, oligodendrocytes, and ependymal cells, account for almost 80% of primary malignant brain tumors in adults [1][2][3][4][5][6]. The incidence and mortality rate associated with gliomas are expected to increase dramatically in the upcoming years, particularly in developing countries [4].…”

“…Due to unfavorable pharmacokinetics of chemotherapeutic drugs, poor drug delivery across the blood-brain barrier (BBB) and blood-tumor barrier (BTB) prevents them from exerting their therapeutic action properly. The inherent chemoresistance of the brain endothelium and glioma cells, expressing the drug efflux protein p-glycoprotein also impairs the therapeutic efficacy [2,3]. Moreover, clinical applications are limited by adverse effects, such as bone marrow suppression, genotoxic, and teratogenic effects [10].…”